These studies represent a continuation of our work in the field of experimental diabetes, pancreatic and islet culture, and islet tissue transplantation. They are designed to investigate the utility of a new technique for the isolation and purification of islet tissue from perinatal sources, as it relates to studies of islet physiology and non-syngeneic transplantability. Advantages inherent in this new technique will be assessed against techniques currently available, and in addition the role of certain cytotoxic byproducts of metabolism as a consequence of standard tissue culture methodology will be examined for their possible role in he alteration of islet tissue immunogenicity. Taking advantage of the selective toxicity of various cell types to products of polyamine oxidation, attempts will be made to design culture conditions which produce purified endocrine tissue. This tissue will be tested in non-syngeneic transplantation models to assess its capacity to permanently reverse experimentally induced diabetes in non-immunosuppressed recipients. Using techniques of immunoassay, ultrastructural analysis, immunocytochemistry, quantitative morphometry, spectrophotometry, chromatography, enzymology and tissue culture, morphological as well as biochemical and physiological parameters can be correlated. These attempts at deriving solutions to the problems of islet supply and non-syngeneic transplantability in experimental animals may hasten the clinical application of islet transplantation to man.